Identification of a BRCA1-mRNA splicing complex required for efficient DNA repair and maintenance of genomic stability.
Bottom Line: Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers.Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery.Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types.
Affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK. Electronic address: firstname.lastname@example.org.Show MeSH
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Mentions: As BRCA1 and BCLAF1 were required for efficient splicing and stability of spliced ATRIP, BACH1, and EXO1 transcripts following DNA damage, we next assessed the effect of BRCA1 or BCLAF1 depletion on ATRIP, BACH1, and EXO1 protein expression. In keeping with the reduced expression of ATRIP, BACH1, and EXO1 spliced transcripts, we observed substantially reduced expression of all three proteins in BRCA1- and BCLAF1-depleted cells following DNA damage (Figure 6A). However, to our surprise, in control cells we did not observe increased levels of ATRIP, BACH1, and EXO1 protein levels following DNA damage that would be expected, given the increased expression of spliced transcript observed. This suggests that either ATRIP, BACH1, and EXO1 translation is attenuated following DNA damage or or that turnover of these proteins may be increased and that BRCA1/BCLAF1-regulated cotranscriptional splicing serves to maintain the expression of these proteins in response to DNA damage.
Affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK. Electronic address: email@example.com.